GeneBe

chr7-2538144-CT-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_152743.4(BRAT1):​c.2390delA​(p.Lys797ArgfsTer84) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,392 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BRAT1
NM_152743.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.744

Publications

0 publications found
Variant links:
Genes affected
BRAT1 (HGNC:21701): (BRCA1 associated ATM activator 1) The protein encoded by this ubiquitously expressed gene interacts with the tumor suppressing BRCA1 (breast cancer 1) protein and and the ATM (ataxia telangiectasia mutated) protein. ATM is thought to be a master controller of cell cycle checkpoint signalling pathways that are required for cellular responses to DNA damage such as double-strand breaks that are induced by ionizing radiation and complexes with BRCA1 in the multi-protein complex BASC (BRAC1-associated genome surveillance complex). The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. [provided by RefSeq, Mar 2012]
BRAT1 Gene-Disease associations (from GenCC):
  • neonatal-onset encephalopathy with rigidity and seizures
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
  • neurodevelopmental disorder with cerebellar atrophy and with or without seizures
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0308 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRAT1NM_152743.4 linkc.2390delA p.Lys797ArgfsTer84 frameshift_variant Exon 14 of 14 ENST00000340611.9 NP_689956.2 Q6PJG6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRAT1ENST00000340611.9 linkc.2390delA p.Lys797ArgfsTer84 frameshift_variant Exon 14 of 14 1 NM_152743.4 ENSP00000339637.4 Q6PJG6-1
BRAT1ENST00000467558.5 linkn.4176delA non_coding_transcript_exon_variant Exon 10 of 10 5
BRAT1ENST00000469750.5 linkn.4962delA non_coding_transcript_exon_variant Exon 11 of 11 2
BRAT1ENST00000493232.5 linkn.5096delA non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456392
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
723574
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33404
American (AMR)
AF:
0.00
AC:
0
AN:
44600
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26084
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39538
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86088
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51988
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1108838
Other (OTH)
AF:
0.00
AC:
0
AN:
60100
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1778824262; hg19: chr7-2577778; API